当前位置:
X-MOL 学术
›
Invertebr. Neurosci.
›
论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Lidocaine and carbamazepine inhibit while phenytoin and lamotrigine paradoxically enhance the insect neuromuscular transmission.
Invertebrate Neuroscience Pub Date : 2019-02-08 , DOI: 10.1007/s10158-019-0224-z Irina M Fedorova 1 , Denis B Tikhonov 1
Invertebrate Neuroscience Pub Date : 2019-02-08 , DOI: 10.1007/s10158-019-0224-z Irina M Fedorova 1 , Denis B Tikhonov 1
Affiliation
Primary mechanism of action of local anesthetics and various anticonvulsants is the voltage-gated sodium channel block. Many of these small molecules also have other targets in nervous system of vertebrates. However, little is known about their action on invertebrate nervous system. Nevertheless, insect-based models are suggested for high-throughput screening of antiepileptic drugs. In the present work, we characterized action of lidocaine, carbamazepine, lamotrigine, and phenytoin on the neuromuscular transition of Calliphora vicina fly larvae using conventional voltage-clamp approach. Carbamazepine and lidocaine caused inhibition of synaptic transmission, which has presynaptic origin. This action is in agreement with inhibition of voltage-gated sodium channels that reduces depolarization of nerve terminals and, thus, calcium entry. Surprisingly, phenytoin and lamotrigine produced a prominent increase in the evoked postsynaptic currents without any effect on frequency or amplitude of spontaneous miniature currents. Potassium channel blocker 4-aminopyridine affects synaptic transmission in similar way. Elevation of synaptic quantal content via increase in calcium concentration or via application of 1 mM 4-aminopyridine eliminates the enhancement effect or even turns it to modest inhibition. We propose that lamotrigine and phenytoin act as inhibitors of insect potassium channels that cause the membrane depolarization and thus facilitates calcium entry into the nerve terminal.
中文翻译:
利多卡因和卡马西平具有抑制作用,而苯妥英钠和拉莫三嗪反常增强昆虫的神经肌肉传递。
局麻药和各种抗惊厥药的主要作用机理是电压门控钠通道阻滞。这些小分子中的许多在脊椎动物的神经系统中也具有其他靶标。然而,关于它们对无脊椎动物神经系统的作用知之甚少。然而,建议使用基于昆虫的模型对抗癫痫药进行高通量筛选。在目前的工作中,我们表征了利多卡因,卡马西平,拉莫三嗪和苯妥英钠对维氏Calliphora的神经肌肉转变的作用。飞蝇幼虫使用常规的电压钳方法。卡马西平和利多卡因引起突触传递的抑制,其具有突触前的起源。该作用与抑制电压门控的钠通道一致,钠通道减少了神经末梢的去极化,从而减少了钙的进入。出人意料的是,苯妥英钠和拉莫三嗪在诱发的突触后电流中显着增加,而对自发性微型电流的频率或幅度没有任何影响。钾通道阻滞剂4-氨基吡啶以类似方式影响突触传递。通过增加钙浓度或通过施加1 mM 4-氨基吡啶来提高突触定量含量,可以消除增强作用,甚至将其变为适度的抑制作用。
更新日期:2019-02-08
中文翻译:
利多卡因和卡马西平具有抑制作用,而苯妥英钠和拉莫三嗪反常增强昆虫的神经肌肉传递。
局麻药和各种抗惊厥药的主要作用机理是电压门控钠通道阻滞。这些小分子中的许多在脊椎动物的神经系统中也具有其他靶标。然而,关于它们对无脊椎动物神经系统的作用知之甚少。然而,建议使用基于昆虫的模型对抗癫痫药进行高通量筛选。在目前的工作中,我们表征了利多卡因,卡马西平,拉莫三嗪和苯妥英钠对维氏Calliphora的神经肌肉转变的作用。飞蝇幼虫使用常规的电压钳方法。卡马西平和利多卡因引起突触传递的抑制,其具有突触前的起源。该作用与抑制电压门控的钠通道一致,钠通道减少了神经末梢的去极化,从而减少了钙的进入。出人意料的是,苯妥英钠和拉莫三嗪在诱发的突触后电流中显着增加,而对自发性微型电流的频率或幅度没有任何影响。钾通道阻滞剂4-氨基吡啶以类似方式影响突触传递。通过增加钙浓度或通过施加1 mM 4-氨基吡啶来提高突触定量含量,可以消除增强作用,甚至将其变为适度的抑制作用。